These results suggest that sequence divergence
between modern humans and Neandertals was a
barrier to gene flow in some regions of the genome and was associated with deleterious fitness consequences (14).

We next leveraged the catalog of introgressedsequences in East Asians and Europeans to re-fine admixture models and infer parameters ofgene flow between modern humans and Nean-dertals (figs. S14 and S15). Specifically, withthe use of an approximate Bayesian compu-tation framework (10), we statistically tested amodel with a single pulse of introgression intothe common ancestor of Europeans and EastAsians (3), as well as a second model with geneflow both in the common ancestor and a second,smaller pulse into East Asians shortly after thetwo populations split (Fig. 3A). Consistent withrecent inferences (5, 9), observed patterns of in-trogression were incompatible with a one-pulsemodel (Fig. 3B), suggesting that gene flow be-tween Neandertals and humans occurred multipletimes. Although we varied many parameters ofeach model (10) (fig. S14), only the ratio of an-cestral effective population size between Euro-peans and East Asians (NeEUR/NeASN) and therelative amount of introgression between thesecond and first pulse (m2/m1) had appreciableeffects on model fit (Fig. 3B). We estimate that